Samuel Cohen, M.D. Ph.D.
Phone: 402.559.6388
Email:
scohen@unmc.edu
Interests:
Chemical Carcinogenesis
Toxicology and Risk Assessment
Surgical Pathology
Urologic Pathology
Research
My research involves several aspects of carcinogenesis, with an emphasis on the urinary bladder as a model
system in rodents and extrapolation between rodent models and the human disease.
We have postulated that agents increase cancer risk by either directly interacting with DNA or increasing
cell proliferation in appropriate target cells in a tissue allowing for more opportunity for spontaneous
mutations to occur during DNA replication.
Genotoxic chemicals, such as nitrofurons, nitrosamines, and acrolein, are evaluated for metabolic activation,
DNA adduct formation, and mutagenesis.
Numerous nongenotoxic chemicals have been identified as enhancing rat bladder carcinogenesis by increasing
urothelial cell proliferation, including arsenic, sodium salts, amino acids, calculus-forming chemicals,
and phenolic chemicals. Increased proliferation occurs either by direct mitogenesis, such as by high doses
of propoxur, or by cellular toxicity and consequent regenerative hyperplasia, such as occurs with formation
of calculi by chemicals like uracil, or by processes involving more subtle cytotoxicity, such as following
high doses of sodium saccharin or arsenic.
We successfully demonstrated the mode of action of sodium saccharin and related sodium salts. Based on
our investigations, it is unlikely that these pose a carcinogenic hazard to humans. Studies with these
salts involve various aspects of toxicology, basic chemistry, cell kinetics, electron microscopy,
pathology, in vitro and in vivo bioassays, renal physiology and molecular biology. These findings led
to the delisting of saccharin from the National Toxicology Program’s List of Carcinogens.
More recently we have investigated the bladder carcinogenicity of dimethylarsinic acid (DMA), an organic
arsenical, in a rat model and in cell culture. DMA and its metabolites are non-DNA reactive, but DMA in
the diet produces urothelial necrosis with consequent regeneration. Urotholial cytotoxicity is produced
in vitro at less than 1 mM concentration of arsenite and 1 mM DMAIII. Urinary levels of DMAIII following
carcinogenic doses of DMA suggest that it may be critical to the urothelial toxicity in vivo. The
relationship to growth factors, receptors, and cell cycle control mechanisms is being evaluated.
Education and Training
B.S. (Honors) University of Wisconsin, 1967
M.D., Ph.D. (Oncology) University of Wisconsin, 1972
Residency, St. Vincent Hospital, 1972-1975
Board Certified in Anatomic and Clinical Pathology, 1976.
National Activities
President, Carcinogenesis Specialty Section, Soc. of Toxicology
Editorial Board or Associate Editor: Lab. Invest., Fd. Chem. Toxicol., Toxicol Sciences, Int. J. Oncology,
Urologic Oncology, Toxicol. Pathol., Intl. Pathol.
Advisory Panels: Chem. Indust. Insti Toxicol.; Int Life Sci Inst – Health and Environmental Sciences
Institute and Risk Sci. Inst.; National Toxicology Program Board of Scientific Counselors; WHO-IPCS
Expert Panel on Carcinogens; Expert Panel of the Flavors and Extracts Manufacturers Association.
